Chemically, zolpidem is N,N,6-trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-acetamide of Formula I. It is commercially available in the form of zolpidem tartrate and marketed as Ambien® and Ambien CR® tablet dosage forms. Zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines, or other drugs with known hypnotic properties.

In contrast to the benzodiazepines (BZ), which non-selectively bind to and activate all BZ receptor subtypes, zolpidem in vitro binds the (BZ)1 receptor preferentially with a high affinity ratio of the α1-subunits/ α5-subunits. The (BZ), receptor is found primarily on the Lamina IV of the sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellummolecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. This selective binding of zolpidem on the (BZ)1 receptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses.
Pharmacokinetic and pharmacodynamic data show that zolpidem has both a rapid absorption and onset of hypnotic action. Its bioavailability is 70% following oral administration and demonstrates linear kinetics in the therapeutical dose range, which lies between 5 and 10 mg in conventional forms, peak plasma concentration is reached at between 0.5 and 3 hours, the elimination half-life is short, with a mean of 2.4 hours and duration of action of up to 6 hours.
Initially, only immediate release dosage forms of zolpidem were developed, which disintegrate and dissolve rapidly in the gastrointestinal tract and undergo systemic absorption, where zolpidem, can exert its pharmacological effect and induce sleep of the patient. The controlled release dosage forms of zolpidem were developed later, which enable to sustain release of zolpidem over a period compatible with the desired time of sleep and the time needed for elimination of the drug from the human body to a sufficiently low level.
Commercially available controlled release tablets of Ambien CR® consists of a coated two-layer tablet, where one layer releases its drug content immediately and the another layer allows a slower release of additional drug content.
EP 173,928 discloses an oral pharmaceutical controlled release preparation which has a biphasic release profile of a pharmacologically active agent, comprising a core containing the active agent and a coating applied thereon, wherein the coating consists of a film-forming polymer which is insoluble in water and gastro-intestinal fluids and a water-soluble pore-creating material also including the active agent.
EP 361,910 discloses granules, which have a spray-dried substance carrying an adsorbed pharmaceutical and a layer comprising a pharmaceutically acceptable excipient and a pharmaceutical.
GB 2,245,492 discloses an orally administrable programmed release pharmaceutical preparation comprising a core coated with a hydrophobic material and a surfactant.
U.S. Pat. No. 6,514,531 describes controlled release dosage forms adapted to release zolpidem or a salt thereof over a predetermined time period, according to a biphasic in vitro profile of dissolution, where the first phase is an immediate release phase having a maximum duration of 30 minutes and the second phase is a prolonged release phase, and wherein 40 to 70% of the total amount of zolpidem is released during the immediate release phase and the time for release of 90% of the total amount of zolpidem is between 2 and 6 hours.
Several other pharmaceutical compositions containing zolpidem have been reported for example, in U.S. Pat. Nos. 6,638,535; 6,500,459; US Application Nos. 2004258750; 2003165566; 2004185097; 2005008702; and International (PCT) Publication Nos. WO2005115345; WO2006010640; and WO2006008636.